Comparison of Three Tocopherol Analogs as an Inhibitor of Production of Proinflammatory Mediators in Macrophages

抄録

Anti-inflammatory effects of tocopherol (TOL) analogs have been attributed to their potent antioxidant activities. However, we and others have separately reported that γTOL or α-tocopheryl succinate (αTOS), despite their lower antioxidant activities, inhibit lipopolysaccharide (LPS)-induced production of prostaglandin E₂ (PGE₂) in macrophages and lung epithelial cells more effectively than αTOL. In the present study, we sought to directly analyze the effect of three TOL analogs (αTOL, αTOS, and γTOL) on LPS-induced production of pro-inflammatory mediators in macrophages. Our data demonstrated that the inhibitory effects of all three TOL analogs on nitric oxide production were very limited. In contrast, αTOS dose-dependently and significantly inhibited LPS-induced PGE₂ production in both RAW264.7 cells and peritoneal macrophages, whereas αTOL and γTOL were much less effective. Although αTOS had no effect on LPS-induced cyclooxygenase-2 expression, it did inhibit COX activity in intact cells. αTOS in combination with sulforaphane, a compound that blocked LPS-induced COX-2 expression, cooperatively and more significantly inhibited PGE₂ production. These findings suggest that αTOS is a more potent inhibitor of the pro-inflammatory mediator PGE₂. The inclusion of αTOS in vitamin supplements may further enhance the effectiveness of strategies for preventing diseases associated with inflammation.